The selective degeneration of retinal capillary pericytes has been well established as the hallmark of diabetic retinopathy. Because this pericyte loss proceeds to any other morphological changes, preventing this pericyte death can be a key to prevent the whole process of diabetic retinopathy. The similar pericyte loss also occurs in dog fed with galactose. Since aldose reductase inhibitors prevent these early capillary changes, aldose reductase has been suggested to involve in this early stage of pericyte degeneration. In this project, we investigated whether inhibition of aldose reductase can prevent the cell death (apoptosis) of retinal capillary pericytes induced by hyperglycemia or galactosemia.When cultured in the medium containing a high concentration (50 mM) of D-galactose, dog retinal capillary cells quickly accumulated sugar alcohol, galactitol. Although the culture in high galactose media was continued for 2 weeks, these cells developed no obvious morphological changes. However, despite of normal morphology, many of the cells displayed positive staining for apoptosis with in situ TUNNEL staining. These cells also displayed the obvious DNA fragmentation called ladder formation. Aldose reductase inhibitor AL 1576 completely prevented all these DNA changes. Interestingly, the similar culture in high galactose medium did not develop any apoptotic changes in dog retinal capillary endothelial cells where the aldose reductase level is extremely low. The presence of aldose reductase appears to be crucial for the induction of apoptosis by the exposure to high sugar environment. - diabetes, retinopathy, aldose reductase, pericyte, endothelial cells, apoptosis